Heart and Stroke Foundation Center for Stroke Recovery

Canada

Heart and Stroke Foundation Center for Stroke Recovery

Canada
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Cordova C.A.,Memorial University of Newfoundland | Cordova C.A.,Heart and Stroke Foundation Center for Stroke Recovery | Jackson D.,Memorial University of Newfoundland | Langdon K.D.,Memorial University of Newfoundland | And 6 more authors.
Behavioural Brain Research | Year: 2014

Small (lacunar) infarcts frequently arise in frontal and midline thalamic regions in the absence of major stroke. Damage to these areas often leads to impairment of executive function likely as a result of interrupting connections of the prefrontal cortex. Thus, patients experience frontal-like symptoms such as impaired ability to shift ongoing behavior and attention. In contrast, executive dysfunction has not been demonstrated in rodent models of stroke, thereby limiting the development of potential therapies for human executive dysfunction. Male Sprague-Dawley rats (n = 40) underwent either sham surgery or bilateral endothelin-1 injections in the mediodorsal nucleus of the thalamus or in the medial prefrontal cortex. Executive function was assessed using a rodent attention set shifting test that requires animals to shift attention to stimuli in different stimulus dimensions. Medial prefrontal cortex ischemia impaired attention shift performance between different stimulus dimensions while sparing stimulus discrimination and attention shifts within a stimulus dimension, indicating a selective attention set-shift deficit. Rats with mediodorsal thalamic lacunar damage did not exhibit a cognitive impairment relative to sham controls. The selective attention set shift impairment observed in this study is consistent with clinical data demonstrating selective executive disorders following stroke within specific sub-regions of frontal cortex. These data contribute to the development and validation of a preclinical animal model of executive dysfunction, that can be employed to identify potential therapies for ameloriating cognitive deficits following stroke. © 2013 Elsevier B.V.


Bolton D.A.E.,University of Waterloo | Bolton D.A.E.,Heart and Stroke Foundation Center for Stroke Recovery | Staines W.R.,University of Waterloo | Staines W.R.,Heart and Stroke Foundation Center for Stroke Recovery
Neuropsychologia | Year: 2012

Normal aging has been linked to impairments in gating of irrelevant sensory information and neural markers of diminished cognitive processing. Whilst much of the research in this area has focussed on visual and auditory modalities it is unclear to what degree these findings apply to somatosensation. Therefore we investigated how age impacts early event-related potentials (ERPs) arising from relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we hypothesised that older adults would demonstrate reduced attention-based modulation of tactile ERPs generated at early stages of cortical somatosensory processing. In accord with previous research we also expected to observe diminished P300 responses to attended targets and behavioural deficits. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only (as instructed) with comparisons between two age groups: (1) Young adults (age range 20-39) and (2) Older adults (age range 62-89). ERP amplitudes for the P50, N70, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at several electrodes (C4, CP4, CP3 and FC4). The P300 in response to attended target stimuli was measured at CPZ. There was no effect of attention on the P50 and N70 however the P100, N140 and LLP were modulated with attention. In both age groups the P100 and LLP were more positive during trials where the stimuli were attended to, whilst the N140 was enhanced for non-attended stimuli. Comparisons between groups revealed a reduction in P100 attention-based modulation for the older adults versus the young adults. This effect was due to a loss of suppression of the non-attended stimuli in older subjects. Moreover, the P300 was both slower and reduced in peak amplitude for older subjects in response to attended targets. Finally, older adults demonstrated impaired performance in terms of both reduced target detection accuracy and in reporting more false positives. Overall, present results reveal a deficit in suppressing irrelevant tactile information during an attention-demanding task which possibly relates to reduced markers of performance. Such a loss of inhibitory function is consistent with age-related change associated with a decline in executive control via prefrontal regions. © 2012 Elsevier Ltd.


Miyasike-Dasilva V.,University of Waterloo | Allard F.,University of Waterloo | McIlroy W.E.,University of Waterloo | McIlroy W.E.,Toronto Rehabilitation Institute | McIlroy W.E.,Heart and Stroke Foundation Center for Stroke Recovery
Experimental Brain Research | Year: 2011

Stair walking is a challenging locomotor task, and visual information about the steps is considered critical to safely walk up and down. Despite the importance of such visual inputs, there remains relatively little information on where gaze is directed during stair walking. The present study investigated the role of vision during stair walking with a specific focus on gaze behaviour relative to (1) detection of transition steps between ground level and stairs, (2) detection of handrails, and (3) the first attempt to climb an unfamiliar set of stairs. Healthy young adults (n = 11) walked up and down a set of stairs with 7 steps (transitions were defined as the two top and bottom steps). Gaze behaviour was recorded using an eye tracker. Although participants spent most part of the time looking at the steps, gaze fixations on stair features covered less than 20% of the stair walking time. There was no difference in the overall number of fixations and fixation time directed towards transitions compared to the middle steps of the stairs. However, as participants approached and walked on the stairs, gaze was within 4 steps ahead of their location. The handrail was rarely the target of gaze fixation. It is noteworthy that these observations were similar even in the very first attempt to walk on the stairs. These results revealed the specific role of gaze behaviour in guiding immediate action and that stair transitions did not demand increased gaze behaviour in comparison with middle steps. These findings may also indicate that individuals may rely on a spatial representation built from previous experience and/or visual information other than gaze fixations (e.g. dynamic gaze sampling, peripheral visual field) to extract information from the surrounding environment. © 2010 Springer-Verlag.


Bolton D.A.E.,University of Waterloo | Bolton D.A.E.,Heart and Stroke Foundation Center for Stroke Recovery | Staines W.R.,University of Waterloo | Staines W.R.,Heart and Stroke Foundation Center for Stroke Recovery
Neuropsychologia | Year: 2011

Damage to the dorsolateral prefrontal cortex (DLPFC) impairs gating of irrelevant sensory information at early cortical processing stages. We investigated how transient inhibition of DLPFC impacts early event-related potentials (ERPs) arising from relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we hypothesized that suppression of DLPFC using continuous theta burst stimulation (cTBS) would result in reduced attention-based modulation of tactile ERPs generated at early stages of cortical somatosensory processing. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only (as instructed) in one of three groups following: (1) cTBS over DLPFC (40 s; 600 pulses of 3 stimuli at 50 Hz repeated at 5 Hz using 80% of resting motor threshold for abductor pollicis brevis), (2) sham stimulation, or (3) no stimulation. ERP amplitudes for the P50, N70, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at C4, CP4, and CP3 electrodes. There was no effect of attention on the P50 and N70 however the P100, N140 and LLP were modulated with attention. The P100 and LLP were significantly more positive during trials where the stimuli were attended to, while the N140 was enhanced for non-attended stimuli. Comparisons between groups revealed a reduction in P100 attention-based modulation for the cTBS group versus sham and no-stimulation groups. While the P100 was clearly reduced for non-attended stimuli relative to attended stimuli in the sham and no-stimulation groups, this effect was attenuated following cTBS. The reduction in attentional modulation of the P100 following cTBS suggests that the DLPFC contributes to filtering irrelevant somatosensory information at early cortical processing stages. Notably the influence of the DLPFC in attention-based modulation was evident even within digits of the same hand. The present results support the use of cTBS as an effective means of transiently suppressing DLPFC excitability. © 2011 Elsevier Ltd.


Mansfield A.,University of Toronto | Mansfield A.,Heart and Stroke Foundation Center for Stroke Recovery | Inness E.L.,University of Toronto | Wong J.S.,University of Toronto | And 4 more authors.
Neurorehabilitation and Neural Repair | Year: 2013

Background. Individuals with stroke fall more often than age-matched controls. Although many focus on the multifactorial nature of falls, the fundamental problem is likely the ability for an individual to generate reactions to recover from a loss of balance. Stepping reactions to recover balance are particularly important to balance recovery, and individuals with stroke have difficulty executing these responses to prevent a fall following a loss of balance. Objective. The purpose of this study is to determine if characteristics of balance recovery steps are related to falls during inpatient stroke rehabilitation. Methods. We conducted a retrospective review of individuals with stroke attending inpatient rehabilitation (n = 136). Details of falls experienced during inpatient rehabilitation were obtained from incident reports, nursing notes, and patient interviews. Stepping reactions were evoked using a "release-from-lean" postural perturbation. Poisson regression was used to determine characteristics of stepping reactions that were related to increased fall frequency relative to length of stay. Results. In all, 20 individuals experienced 29 falls during inpatient rehabilitation. The characteristics of stepping reactions significantly related to increased fall rates were increased frequency of external assistance to prevent a fall to the floor, increased frequency of no-step responses, increased frequency of step responses with inadequate foot clearance, and delayed time to initiate stepping responses. Conclusions. Impaired control of balance recovery steps is related to increased fall rates during inpatient stroke rehabilitation. This study informs the specific features of stepping reactions that can be targeted with physiotherapy intervention during inpatient rehabilitation to improve dynamic stability control and potentially prevent falls. © The Author(s) 2013.


Bolton D.A.E.,University of Waterloo | Bolton D.A.E.,Heart and Stroke Foundation Center for Stroke Recovery | Staines W.R.,University of Waterloo | Staines W.R.,Heart and Stroke Foundation Center for Stroke Recovery
Neuropsychologia | Year: 2014

Objectives: To investigate the role of the prefrontal cortex in attention-based modulation of cortical somatosensory processing. Methods: Six prefrontal stroke patients were compared with eleven neurologically intact older adults during a vibrotactile discrimination task. All subjects attended to stimuli on one digit while ignoring distracter stimuli on a separate digit of the same hand. Subjects were required to report infrequent targets on the attended digit only. Throughout testing electroencephalography was used to measure event-related potentials for both task-relevant and irrelevant stimuli. Results: Prefrontal patients demonstrated significant changes in cortical somatosensory processing based on attention compared to age-matched controls. This was evident both in early unimodal somatosensory processing (i.e. P100) and in later cortical processing stages (i.e. long-latency positivity). Moreover, there was a tendency towards a tonic loss of inhibition over early somatosensory cortical processing (i.e. P50). Conclusions: The attention-based modulation noted for neurologically intact older adults was absent in prefrontal lesion patients. Significance: The present study highlights the important role of prefrontal regions in sustaining inhibition over early sensory cortical processing stages and in modifying somatosensory transmission based on task-relevance. Notably these deficits extend beyond those previously shown to occur as a function of age. © 2014 Elsevier Ltd.


Makedonov I.,Heart and Stroke Foundation Center for Stroke Recovery | Makedonov I.,University of Toronto | Black S.E.,Heart and Stroke Foundation Center for Stroke Recovery | Black S.E.,University of Toronto | And 4 more authors.
European Journal of Neurology | Year: 2013

Background: White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). Methods: Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. Results: WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. Conclusion: Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.


Lake E.M.R.,University of Toronto | Bazzigaluppi P.,University of Toronto | Stefanovic B.,University of Toronto | Stefanovic B.,Sunnybrook Research Institute | Stefanovic B.,Heart and Stroke Foundation Center for Stroke Recovery
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

Ischaemic stroke is the leading cause of adult disability worldwide.Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression.Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression.Stroke affects each of the physiological parameters underlying the BOLD contrast, markedly complicating the interpretation of BOLD fMRI data.This review summarizes current progress on application of BOLD fMRI in the chronic stage of ischaemic injury progression and discusses means by which more information may be gained from such BOLD fMRI measurements.Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function.The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations. © 2016 The Author(s).


Clarke J.,Memorial University of Newfoundland | Clarke J.,Heart and Stroke Foundation Center for Stroke Recovery | Langdon K.D.,Memorial University of Newfoundland | Langdon K.D.,Heart and Stroke Foundation Center for Stroke Recovery | And 4 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2014

Early poststroke rehabilitation effectively improves recovery of function, likely by engaging multiple plasticity processes through use-dependent activation of neural circuits. The loci of such neuroplastic reorganization have not been examined during the initial phase of behavioral recovery. In the current study, we sought to evaluate sub-components of rehabilitation and to identify brain sites first engaged by early rehabilitation. Rats were subjected to endothelin-1 ischemia and placed in either enriched environment (EE), daily reach training (RT), combination of enriched environment and reach training (ER), or standard housing (ST) starting 7 days post ischemia. Functional and histopathological assessments were made after 2, 5, and 10 days of treatment. Animals exposed to 10 days of ER treatment exhibited significantly more use-dependent neuronal activity (FosB/ΔFosB expression) in perilesional cortex than those exposed to EE, RT, or ST treatments. Similar trends were observed in both perilesional striatum and contralesional forelimb motor cortex. This use-dependent plasticity was not explained by differences in neuronal death, inflammation, or lesion volume. The increased activity likely contributes to the neuroplastic changes and functional recovery observed after extended periods of rehabilitation. Importantly, EE or RT alone did not lead to enhanced activity suggesting that combination therapy is necessary to promote maximum recovery. © 2014 ISCBFM All rights reserved.


Al-Khindi T.,University of Toronto | MacDonald R.L.,St Michaels Hospital | MacDonald R.L.,University of Toronto | MacDonald R.L.,Li Ka Shing Knowledge Institute | And 4 more authors.
Stroke | Year: 2010

Background and Purpose-: Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency characterized by the accumulation of blood in the subarachnoid space surrounding the brain. The acute treatment of aSAH is well documented but less is known about the long-term effects of aSAH on cognition and day-to-day functioning. Methods-: We reviewed all studies in the past 10 years that have focused on the effects of aSAH on cognition and day-to-day functioning. Results-: Sixty-one empirical studies examining cognitive and functional outcome in patients with aSAH met inclusion criteria. Survivors of aSAH commonly experience deficits in memory, executive function, and language. These cognitive impairments interact to affect patients' day-to-day functioning, including activities of daily living, instrumental activities of daily living, return to work, and quality of life. Deficits in cognition and day-to-day functioning are further compounded by depression, anxiety, fatigue, and sleep disturbances. Conclusions-: Much remains to be learned about the brain changes underlying cognitive and functional deficits, including the role of diffuse brain damage and secondary complications like vasospasm and elevated intracranial pressure. A consideration of these issues is necessary to obtain a better understanding of how aSAH affects cognition and day-to-day functioning in the long-term. © 2010 American Heart Association, Inc.

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